A COMPARISON OF AZTREONAM AND 2 REGIMENS OF GENTAMICIN IN A RABBIT MODEL OF INTRAAMNIOTIC INFECTION AND SEPSIS

OBJECTIVE: To compare aztreonam in a standard dose with two gentamicin doses in the early treatment of experimental intra-amniotic infection in rabbits induced by intracervical inoculation with Escherichia coli . METHODS: Timed pregnant rabbits on day 21 (70% of gestation) were in oculated intracervically with 10(4)-10(5) colony-forming units of E co li. After inoculation, the animals were treated with one of three regi mens: 1) aztreonam at 90 mg/kg/day (''standard'' dose in humans), 2) g entamicin at 4.5 mg/kg/day (''standard'' dose in humans), or 3) higher -dose gentamicin at 6.0 mg/kg/day, each given in three divided doses d aily. Outcomes included fever, delivery, and presence of a live fetus. At necropsy, cultures were taken from endometrium, amniotic fluid, an d blood. Data were analyzed by Fisher exact test because the expected cell size was fewer than five. RESULTS: Compared with rabbits treated with aztreonam, chose treated with gentamicin 4.5 mg/kg/day delivered significantly move often (P = .002), had move positive cultures (P <.0 01), and had significantly fewer live fetuses (P <.001). Compared with rabbits treated with gentamicin 6.0 mg/kg/day, those treated with gen tamicin 4.5 mg/kg/day delivered move often (P .003), had fewer live fe tuses (P =.02), and had move positive cultures (P = .02). There were n o significant differences between the aztreonam and gentamicin 6.0 mg/ kg/day groups. CONCLUSIONS: This study demonstrates in an animal model that aztreonam and gentamicin at 6.0 mg/kg/day are more effective tha n gentamicin at 4.5 mg/kg/day (a dose that is widely used empirically in humans) in the early treatment of experimental intra-amniotic infec tion in rabbits. Aztreonam was as effective as gentamicin at 6.0 mg/kg /day. In this rabbit model, in which intra-amniotic infection is accom panied by maternal sepsis, 4.5 mg/kg/day of gentamicin was not adequat e for the treatment of severe maternal infection.